At birth, both fetal lung liquid production and pulmonary vascular resistance are rapidly reduced. We have previously shown that mediators of pulmonary vasodilation, including prostaglandins, also cause significant reductions in fetal lung liquid production (J Appl Physiol 1995; 1212). Since cAMP is a known mediator of both lung liquid resorption and of prostaglandin-induced vasorelaxation, we asked whether it might be an important mediator of transitional events at birth. To see if cAMP, at a concentration sufficient to cause significant reduction in lung liquid production, would lower pulmonary resistance, we studied its effects on pulmonary arterial pressure and flow. Eight chronically prepared fetal sheep were studied at 131 ± 5 d gestation. Net lung luminal liquid production(Jv) was measured by plotting the change in lung luminal liquid concentration of radiolabelled albumin, an impermeant tracer that was mixed into the lung liquid at the start of each study. Variables were measured during a 1-2 h baseline, then for 2-3 h following an intratracheal instillation of dibutyryl cAMP (initial concentration ≅10-4 M). Instillation of cAMP reduced Jv from 25 ± 8 ml/h to 4 ± 8 ml/h (P<.001) and pulmonary artery pressure from 46 ± 3 mm Hg to 43± 4 mm Hg (P<.05). There was a modest increase in left pulmonary blood flow (P=.10) such that the calculated pulmonary vascular resistance fell from 0.89 ± 0.24 to 0.66 ± 0.17 mm Hg/ml/min (P<.05). Systemic arterial and left atrial pressures and heart rate did not change significantly following cAMP instillation. Control (saline) instillations(n=6) caused no significant change in any variable.

Cyclic AMP, at lung luminal levels sufficient to reduce fetal lung liquid production, also decreases pulmonary vascular resistance, and may play an important role in the transition of the lung at birth. (Supported by AHA Grant-in-Aid #94-317)